Over the last several years compounds have been reported in the patent and technical literature as possessing in a single molecule both angiotensin converting enzyme (ACE) inhibitory activity and neutral endopeptidase (EC24.11; NEP) inhibition activity. These compounds are of interest as cardiovascular agents particularly in the treatment of hypertension, congestive heart failure, and renal disease. These compounds are also referred to as vasopeptidase, dual metalloprotease, NEP/ACE, or ACE/NEP inhibitors.
Omapatrilat is such a vasopeptidase inhibitor which is currently undergoing clinical evaluation. Omapatrilat has the chemical name [4S-[4.alpha.(R*), 7.alpha., 10a.beta.]]-octahydro-4-[(2-mercapto-1-oxo-3-phenylpropyl)amino]-5-oxo-7H- pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid and the structural formula ##STR1## Omapatrilat, its preparation, and its use in treating cardiovascular diseases are disclosed by Robi in U.S. Pat. No. 5,508,272.
BMS 189,921 is another vasopeptidase inhibitor which is currently undergoing clinical evaluation. BMS 189,921 has the chemical name [S-(R*,R*)]-hexahydro-6-[(2-mercapto-1-oxo-3-phenylpropyl)amino]-2,2-dimet hyl-7-oxo-1H-azepine-1-acetic acid and the structural formula ##STR2## BMS 189,921, it preparation, and its use in treating cardiovascular diseases are disclosed by Karanewsky et al. in U.S. Pat. No. 5,552,397.